Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis)
Condition(s) studied
Investigational drug(s) / intervention(s)
Fazirsiran Injection: Fazirsiran will be injected subcutaneously.
Placebo: Fazirsiran matching placebo.
Study summary
The liver produces a protein called alpha-1 antitrypsin (AAT). AAT is normally released into the bloodstream. In some people, the liver makes an abnormal version of the AAT protein, called Z-AAT. Making an abnormal version of the AAT protein can result in liver disease as Z-AAT builds up in liver cells, which leads to liver problems such as liver scarring (fibrosis), continuing liver damage (cirrhosis), and eventually end stage liver disease. Fazirsiran is a medicine that reduces the creation of the Z-AAT protein and thus the build-up of this abnormal protein in the liver. People with this type of liver disease who already have mild liver scarring will take part in the study. They will be treated with fazirsiran or a placebo for about 2 years. This study will check the long-term safety of fazirsiran, whether participants tolerate the treatment and if there are any effects on liver scarring. A liver biopsy, a way of collecting a small tissue sample from the liver, will be taken twice during the study.
Eligibility
Primary outcome measure(s)
- Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) — From start of study drug administration up to End of study (EOS) (Week 124)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not it is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study intervention. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, suspected transmission of any infectious agent, an important medical event. AEs and SAEs including any pulmonary AEs or SAEs indicative of worsening pulmonary condition (example, pulmonary exacerbation, respiratory infection, significant pulmonary function test decline) will be reported. - Number of Participants With Clinically Significant Change From Baseline in Pulmonary Function Parameters — From start of study drug administration up to EOS (Week 124)
Standard pulmonary function parameters will be used to study lung function. Clinical significance of pulmonary function parameters will be determined at the investigator's discretion. - Change From Baseline in Whole Lung 15th Percentile Density as Measured by Computed Tomography (CT) Lung Densitometry — Baseline up to Week 100
Change from baseline in whole lung 15th percentile density as measured by CT lung densitometry will be assessed. - Number of Participants With Clinically Significant Changes in Vital Signs — From start of study drug administration up to EOS (Week 124)
Vital signs include body temperature, respiratory rate, blood pressure (systolic and diastolic), pulse (beats per minute) and pulse oximetry. Clinical significance of vital signs will be determined at the investigator's discretion. - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters — From start of study drug administration up to EOS (Week 124)
12-lead ECG will be evaluated. Any clinically significant change in ECG assessments will be determined at the investigator's discretion. - Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters — From start of study drug administration up to EOS (Week 124)
Laboratory parameters assessments include hematology, biochemistry including liver tests, coagulation, and urinalysis. Clinical significance of laboratory parameters will be determined at the investigator's discretion.
Trial sites (41)
| Facility | City | Region | Status |
|---|---|---|---|
| St Joseph's Hospital and Medical Center | Phoenix | Arizona | Recruiting |
| Mayo Clinic - PPDS | Phoenix | Arizona | Recruiting |
| University of Arizona Thomas D. Boyer Liver Institute | Tucson | Arizona | Recruiting |
| University of California San Diego | La Jolla | California | Recruiting |
| UCLA Pulmonary and Critical Care | Los Angeles | California | Recruiting |
| University of California Benioff Children's Hospital | San Francisco | California | Recruiting |
| Peak Gastroenterology Associates | Colorado Springs | Colorado | Recruiting |
| Schiff Center for Liver Diseases/University of Miami | Miami | Florida | Recruiting |
| Indiana University School of Medicine-Indianapolis | Indianapolis | Indiana | Recruiting |
| University Of Iowa Hospitals And Clinics | Iowa City | Iowa | Recruiting |
| Boston Medical Center | Boston | Massachusetts | Recruiting |
| University of Michigan Hospital - 1500 E Medical Center Dr | Ann Arbor | Michigan | Recruiting |
| Henry Ford Health System | Novi | Michigan | Recruiting |
| Mayo Clinic PPDS | Rochester | Minnesota | Recruiting |
| NYU Langone Medical Center | New York | New York | Recruiting |
| Columbia University Irving Medical Center | New York | New York | Recruiting |
| University Hospitals Cleveland Medical Center | Cleveland | Ohio | Recruiting |
| Penn State Health Milton S. Hershey Medical Center | Hershey | Pennsylvania | Recruiting |
| Texas Liver Institute American Research Corporation | San Antonio | Texas | Recruiting |
| Bon Secours St. Mary's Hospital | Newport | Virginia | Recruiting |
| LKH-Universitätsklinikum Graz | Graz | Austria | Recruiting |
| KABEG - Klinikum Klagenfurt Am Wörthersee | Klagenfurt | Austria | Recruiting |
| UZ Antwerpen | Antwerp | Belgium | Recruiting |
| UZ Leuven | Leuven | Belgium | Recruiting |
| Inspiration Research Limited | Toronto | Ontario | Recruiting |
| Hôpital de La Croix Rousse | Lyon | France | Recruiting |
| Hopital PONTCHAILLOU CHU de Rennes | Rennes | France | Recruiting |
| Hôpital Paul Brousse | Val-de-Marne | France | Recruiting |
| Universitätsklinikum der RWTH Aachen | Aachen | Germany | Recruiting |
| Charité - Campus Virchow-Klinikum | Berlin | Germany | Recruiting |
| Hannover Medical School | Hanover | Germany | Recruiting |
| Universitätsklinikum Tübingen | Tübingen | Germany | Recruiting |
| Fondazione IRCCS Policlinico San Matteo | Pavia | Italy | Recruiting |
| ID Clinic Arkadiusz Pisula | Mysłowice | Poland | Withdrawn |
| CCA Hospital Braga | Braga | Portugal | Recruiting |
| Hospital Dr. Nélio Mendonça | Funchal | Portugal | Recruiting |
| Centro Hospitalar de Universitário de Santo António E.P.E | Porto | Portugal | Recruiting |
| Hospital Universitario Virgen del Rocio - PPDS | Seville | Spain | Recruiting |
| Karolinska Universitetssjukhuset Huddinge | Huddinge | Sweden | Recruiting |
| Universitätsspital Bern | Bern | Switzerland | Recruiting |
+ 1 more sites — see the full list on the official registry below.
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT06165341 on ClinicalTrials.gov ↗ ← All trials in Spain